Herpes simplex viruses (HSV) establish persistent infections where the viruses modulate host immune systems in a complex way. Although many factors are involved, emerging evidence indicates that the interaction of HSV and dendritic cells is a key step which dictates the outcome of viral infection and pathogenesis. As sentinels, dendritic cells bridges innate and adaptive immunity. It is well documented that upon infection immature dendritic cells take up viral antigens, undergo maturation. In this process, co-stimulatory molecules such as MHC class II, CD40, CD80, and CD86 are up-regulated. Additionally, mature dendritic cells release inflammatory cytokines such as IL-6, IL-12, TNF-?, and type I interferon. These cellular factors coordinate with dendritic cells to control viral infection. Nevertheless, HSV replication compromises dendritic cell functions. Currently, little is known about underlying mechanisms due to the complex nature of HSV life cycles. The objective of this research is to understand the viral mechanisms through which HSV ?134.5 modulate dendritic cell maturation and functions. It is believed that this viral factor perturbs one or more of cellular components of Toll-like related innate signaling pathways in dendritic cells and impairs subsequent T cell activation in HSV infection. As such, multi-faceted approaches will be taken to investigate the roles of viral and cellular elements. Systematic analysis will be carried out to define critical functional domains in the context of viral replication and the induction of co-stimulatory molecules and cytokines. Additionally, studies will be performed to examine components and the nature of HSV and dendritic cell interactions relevant to viral pathogenesis. Together, these studies will not only advance our understanding of the mechanisms of viral infection but also provide an insight into dendritic cell functions in viral infections.
Herpes simplex viruses are human pathogens that cause diseases such as genital herpes, keratitis, blindness, and encephalitis. Herpes simplex virus infection is also a risk factor in HIV transmission. This research is designed to investigate how herpes simplex viruses impair the functions of immune cells which restrict viral infections. The proposed research may facilitate the development of novel vaccines and antiviral therapeutics.
|Ma, Yijie; He, Bin (2014) Recognition of herpes simplex viruses: toll-like receptors and beyond. J Mol Biol 426:1133-47|
|Lei, Xiaobo; Han, Ning; Xiao, Xia et al. (2014) Enterovirus 71 3C inhibits cytokine expression through cleavage of the TAK1/TAB1/TAB2/TAB3 complex. J Virol 88:9830-41|
|Xiang, Zichun; Li, Linlin; Lei, Xiaobo et al. (2014) Enterovirus 68 3C protease cleaves TRIF to attenuate antiviral responses mediated by Toll-like receptor 3. J Virol 88:6650-9|
|Wang, Yu; Yang, Yin; Wu, Songfang et al. (2014) p32 is a novel target for viral protein ICP34.5 of herpes simplex virus type 1 and facilitates viral nuclear egress. J Biol Chem 289:35795-805|
|Lei, Xiaobo; Xiao, Xia; Xue, Qinghua et al. (2013) Cleavage of interferon regulatory factor 7 by enterovirus 71 3C suppresses cellular responses. J Virol 87:1690-8|
|Jin, Huali; Ma, Yijie; Yan, Zhipeng et al. (2012) Activation of NF-ÎºB in CD8+ dendritic cells Ex Vivo by the Î³134.5 null mutant correlates with immunity against herpes simplex virus 1. J Virol 86:1059-68|
|Ma, Yijie; Jin, Huali; Valyi-Nagy, Tibor et al. (2012) Inhibition of TANK binding kinase 1 by herpes simplex virus 1 facilitates productive infection. J Virol 86:2188-96|
|Lei, Xiaobo; Sun, Zhenmin; Liu, Xinlei et al. (2011) Cleavage of the adaptor protein TRIF by enterovirus 71 3C inhibits antiviral responses mediated by Toll-like receptor 3. J Virol 85:8811-8|
|Li, Yapeng; Zhang, Cuizhu; Chen, Xiangdong et al. (2011) ICP34.5 protein of herpes simplex virus facilitates the initiation of protein translation by bridging eukaryotic initiation factor 2alpha (eIF2alpha) and protein phosphatase 1. J Biol Chem 286:24785-92|
|Jin, Huali; Yan, Zhipeng; Ma, Yijie et al. (2011) A herpesvirus virulence factor inhibits dendritic cell maturation through protein phosphatase 1 and Ikappa B kinase. J Virol 85:3397-407|
Showing the most recent 10 out of 11 publications